FDA EIR - Covance Laboratories Inc. - July 26, 2017

An FDA inspection was conducted at Covance Inc., Princeton, NJ, from July 17 to July 26, 2017. The inspection focused on Covance's role as a Contract Research Organization (CRO) for New Drug Applications involving ertugliflozin studies (P001/B1521016 and P006/B1521015), assessing adherence to principles of good clinical practice. No formal Inspectional Observations (Form FDA-483) were issued. However, during the close-out meeting, the inspector discussed several findings and recommendations with Covance management. One key finding concerned electronic records; specifically, the printouts of certain electronic data did not explicitly include electronic signatures. While audit trails confirming review and approval existed and were deemed adequate, the inspector emphasized the importance of ensuring all data, including signature details, are clearly represented in provided documentation. Covance agreed to this point. Issues related to clinical study randomization were also discussed. For Protocol 001, a significant number of subjects were incorrectly stratified during randomization, partly due to broad definitions in the protocol and errors at clinical sites. The randomization system's limitation in identifying multi-enrolled subjects across different sites also led to several participants being randomized at multiple locations. The inspector noted that randomization activities were contracted by the Sponsor and typically not managed by Covance. Despite this, Covance was encouraged to discuss these randomization system limitations and protocol clarity issues with the Sponsor to implement more robust cross-checks and provide clearer guidance to clinical sites to prevent future occurrences of mis-stratification and multiple enrollments. Covance management acknowledged these points.